{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:55:04Z","timestamp":1787313304706,"version":"build-2736575974"},"reference-count":60,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82374454"],"award-info":[{"award-number":["82374454"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82260938"],"award-info":[{"award-number":["82260938"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010857","name":"Jiangxi Provincial Department of Science and Technology","doi-asserted-by":"publisher","award":["2023KZI01001"],"award-info":[{"award-number":["2023KZI01001"]}],"id":[{"id":"10.13039\/501100010857","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Inflammatory bowel disease (IBD) and metabolic syndrome (MetS) exhibit a complex interplay, with clinical evidence indicating an increasing incidence of their co-occurrence. However, current research lacks a systematic framework to model the pleiotropic genetic architecture linking gastrointestinal and liver-metabolic phenotypes, thereby hindering a comprehensive understanding of how multiple genetic risk factors converge to drive IBD\u2013MetS comorbidity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study employed genomic structural equation modeling (SEM) to integrate genome-wide association study (GWAS) summary datasets for IBD and MetS-related traits (body mass index, triglycerides, non-alcoholic fatty liver disease, hypertension, and type 2 diabetes), creating the multivariate GWAS summary datasets. Post-GWAS analytical approaches were subsequently utilized to assess risky loci, gene functionality, and tissue-specific regulatory networks, aiming to elucidate the pathological connections between chronic low-grade inflammation and the gut-liver-metabolic axis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Genomic SEM identified a shared latent genetic factor between IBD and MetS (Comparative Fit Index\u2009=\u20090.9864, Standardized Root Mean Square Residual\u2009=\u20090.0602). A total of 522 lead single nucleotide polymorphism (SNP) loci were identified, including 21 novel SNPs specific to the multivariate model that were not detected in univariate GWAS. Fine-mapping with SuSiE and FINEMAP identified 29 high-confidence causal SNPs. Integrating SNP fine-mapping with MAGMA, FUSION, and FOCUS analyses confirmed seven core genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>To the best of our knowledge, this study provides the first comprehensive characterization of the shared genetic architecture of IBD and MetS through a multivariate genetic model. The results deepen the understanding of the genetic mechanisms underlying IBD and MetS and offer potential therapeutic targets and a conceptual framework for developing interventions for cross-system diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0334456","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T17:31:41Z","timestamp":1760635901000},"page":"e0334456","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Investigating the common genetic basis between inflammatory bowel disease and metabolic syndrome through genomic structural equation modeling"],"prefix":"10.1371","volume":"20","author":[{"given":"Pan","family":"Shen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing-Hua","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Fan","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wu","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9503-8267","authenticated-orcid":true,"given":"Lei-Chang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,10,16]]},"reference":[{"issue":"7351","key":"pone.0334456.ref001","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1038\/nature10209","article-title":"Genetics and pathogenesis of inflammatory bowel disease","volume":"474","author":"B Khor","year":"2011","journal-title":"Nature"},{"key":"pone.0334456.ref002","first-page":"237","article-title":"A clinical review of recent findings in the epidemiology of inflammatory bowel disease","volume":"5","author":"A Ponder","year":"2013","journal-title":"Clin Epidemiol"},{"key":"pone.0334456.ref003","doi-asserted-by":"crossref","first-page":"8646495","DOI":"10.1155\/2017\/8646495","article-title":"Nutrition and IBD: malnutrition and\/or sarcopenia? 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